Endocytosis and subcellular localization of transforming growth factor-β (TGF-β) receptors have been shown to modulate TGF-β signaling by controlling receptors activity and stability.Two major endocytic pathways have been reported to mediate the internalization of TGF-β receptors with opposite effects on TGF-β signaling:clathrin-mediated endocytosis promotes it whereas lipid rafts/caveolae-mediated endocytosis inhibits it.We have identified several factors that regulate the internalization of TGF-β receptors via the two different routes.We have also obtained the evidence that the clathrin-and caveolae-mediated endocytic pathways can be fused during TGF-β receptor endocytic trafficking.Our data provide a possible novel scenario of TGF-β receptor endocytosis that generates the multifunctional sorting device-caveolin-1-positive early endosomes to orchestrate TGF-β signaling.